A sustained-release drug delivery system for contraceptive progestins may be obtained by impregnating the steroid in an intrauterine device (IUD). The device, which is also called "uterine progestin system (UPS)", will release, in the uterine cavity, a small amount of progestin at a controlled rate for a period of several months. This project is designed to study the basic mechanisms involved in the uterine uptake and retention of contraceptive progestins administered through UPS so as to assess the overall bioavailability of contraceptive progestins in this particular route of administration. Various physiological factors, such as the estrous cycle, uterine progestin receptors, and plasma progestin binding macromolecules, will also be studied to ascertain any effect these may have on the extent and rate of uterine absorption, retention, and distribution of contraceptive progestins administered by the intraluminal route. The areas of research proposed in this project are: (1), the pharmacokinetics involved in the absorption, retention, and distribution of contraceptive progestins upon intrauterine administration; (2), the possible roles uterine progesterone receptors may play on the absorption, retention, disposition, and the overall action of contraceptive progestins administered by the intraluminal route; (3), the long-term effect on progestin receptors, both quantitative and qualitative, upon chronic exposure of uterine tissues to various contraceptive progestins in vivo; and (4), the interplay between serum progestin-binding macromolecules and uterine progestin receptors on the overall distribution and pharmacodynamics of progestins in the uterus.